Invasive aspergillosis caused by Aspergillus terreus: an emerging opportunistic infection with poor outcome independent of azole therapy

J Antimicrob Chemother. 2014 Nov;69(11):3148-55. doi: 10.1093/jac/dku241. Epub 2014 Jul 8.

Abstract

Objectives: Invasive aspergillosis (IA) caused by Aspergillus terreus is a significant cause of morbidity and mortality in patients with haematological malignancy (HM). Very few data are available in this patient population to differentiate IA patients with A. terreus from those with non-terreus species of Aspergillus to compare outcomes. We retrospectively investigated 513 HM patients who were treated for either definite or probable IA between June 1993 and August 2012 in a cancer centre.

Methods: We compared baseline characteristics, antifungal therapies and outcomes between patients infected with A. terreus (n = 96, 18.7%) and those infected with non-terreus Aspergillus species (n = 335, 65.3%). Eighty-one patients with mixed or unspecified Aspergillus infections were excluded.

Results: Breakthrough infections occurred more frequently in the A. terreus group (91% versus 77%, P = 0.009). A. terreus infection was associated with a lower rate of final response to antifungal therapy (21% versus 38%, P = 0.0015) and a higher rate of IA-associated mortality (51% versus 30%, P < 0.001). Multivariate analyses showed that these associations were independent of patients' clinical characteristics and the antifungal regimens they received. Factors independently associated with final response included treatment with azoles (OR 3.1, 95% CI 1.9-5.0, P < 0.0001) and Aspergillus species (A. terreus versus non-terreus Aspergillus species) (OR 0.5, 95% CI 0.3-0.98, P = 0.043). Additionally, Aspergillus species and treatment with azoles were independently associated with IA-associated mortality.

Conclusions: A. terreus IA in HM patients was associated with worse outcome than IA caused by non-terreus Aspergillus species. Poor prognosis in patients with invasive A. terreus infections is independent of anti-Aspergillus azole-based treatment.

Keywords: A. terreus; IA; haematological malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / drug therapy*
  • Aspergillosis / epidemiology
  • Aspergillus / drug effects
  • Aspergillus / isolation & purification*
  • Azoles / pharmacology
  • Azoles / therapeutic use
  • Child
  • Female
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Opportunistic Infections / drug therapy*
  • Opportunistic Infections / epidemiology
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Antifungal Agents
  • Azoles